title: Genetic polymorphisms and other risk factors associated with bisphosphonate induced osteonecrosis of the jaw.
abstract: Bisphosphonate induced osteonecrosis of the jaw (BONJ) is a complication in patients taking bisphosphonate (BP) that affects their quality of life and compliance. In this cohort study, patients with multiple myeloma (MM) on intravenous BP therapy were enrolled over 1 year. Demographic and clinical data and genotyping of 10 single nucleotide polymorphisms (SNPs) from seven candidate genes associated with drug or bone metabolism were determined. Of the 78 patients enrolled, 12 had BONJ. The median time to developing BONJ was 28 months. Univariate and multivariate analysis revealed a significant association between BONJ and smoking (p=0.048) and type of BP treatment (p=0.03). A trend for higher odds for BONJ was found for SNPs in five genes: COL1A1 (rs1800012), RANK (rs12458117), MMP2 (rs243865), OPG (rs2073618) and OPN (rs11730582). Considering all five SNPs together, patients with genotype scores ≥ 5 had a BONJ event rate of 57%; those with scores < 5 had a rate of 10%. The adjusted odds ratio was 11.2 (95% confidence interval of 1.8-69.9; p value 0.0097). Smoking, type of BP and combined genotype score of COL1A1, RANK, MMP2, OPG and OPN were significantly associated with BONJ in MM patients undergoing BP therapy.
authors.affiliation: Department of Oral Medicine, College of Dentistry, University of Florida, Gainesville, USA. jkatz@dental.ufl.edu
authors.forename: J
authors.initials: J
authors.lastname: Katz
authors.forename: Y
authors.initials: Y
authors.lastname: Gong
authors.forename: D
authors.initials: D
authors.lastname: Salmasinia
authors.forename: W
authors.initials: W
authors.lastname: Hou
authors.forename: B
authors.initials: B
authors.lastname: Burkley
authors.forename: P
authors.initials: P
authors.lastname: Ferreira
authors.forename: O
authors.initials: O
authors.lastname: Casanova
authors.forename: T Y
authors.initials: TY
authors.lastname: Langaee
authors.forename: J S
authors.initials: JS
authors.lastname: Moreb
mesh_terms: D000328:Adult; D000368:Aged; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000009:adverse effects*; D015331:Cohort Studies; D024042:Collagen Type I / Q000235:genetics; D000090602:Collagen Type I, alpha 1 Chain; D065727:Cytochrome P-450 CYP2C8; D004164:Diphosphonates / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000009:adverse effects; D007275:Injections, Intravenous; D007571:Jaw Diseases / Q000139:chemically induced* / Q000235:genetics; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy; D010020:Osteonecrosis / Q000139:chemically induced* / Q000235:genetics; D053495:Osteopontin / Q000235:genetics; D053244:Osteoprotegerin / Q000235:genetics; D000077268:Pamidronate; D011110:Polymorphism, Genetic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000235:genetics; D012307:Risk Factors; D012907:Smoking; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D004164:Diphosphonates; D007093:Imidazoles; D053244:Osteoprotegerin; D053246:Receptor Activator of Nuclear Factor-kappa B; C505686:TNFRSF11A protein, human; D014409:Tumor Necrosis Factor-alpha; D053495:Osteopontin; D000077211:Zoledronic Acid; D001189:Aryl Hydrocarbon Hydroxylases; C450259:CYP2C8 protein, human; D065727:Cytochrome P-450 CYP2C8; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D000077268:Pamidronate